The use of cytokines as adjuvants has been shown to be a promising approach for enhancing DNA vaccine induced-immune responses. In this report, we investigate the administration of cytokines to modulate both humoral and cell-mediated immune responses elicited by an HCV-core plasmid DNA vaccine in Balb/c mice. Our studies indicate that the HCV-core DNA vaccine has been able to induce both antibody and cellular immunity in a DNA prime-protein boost regimen. GM-CSF (granulocyte-monocyte colony stimulating factor) which is considered to be a cytokine displaying both Th1 and Th2 characteristics, and plays an important role in augmenting antibody and cell-mediated immunity was also administered. The induction of cellular immunity was not as striking as humoral immunity in this case. To obtain a stronger cellular response, IL-23, a Th1 cytokine belonging to the IL-12 family, was also included in the regimen. Spleen cell proliferation, IFN-gamma production from spleen cells and specific serum IgG2a, all demonstrate the enhancement of cell-mediated immunity without any observable suppressive effect on antibody and humoral immune responses. We also examined the timing of plasmid IL-23 administration on the phenotype of the resultant T cell responses in a 3 day interval, before and after plasmid GM-CSF administration. The results did not indicate any change in the Th1/Th2 balance as compared with simultaneous IL-23 administration.